1994 年度実績報告書

発癌過程ならびに癌細胞形質の発現におけるプロテインホスファターゼの意義

研究課題

研究課題/領域番号	06281101
研究機関	北海道大学
研究代表者	菊地九二三北海道大学, 免疫科学研究所, 教授 (20006117)
研究分担者	日野田裕治札幌医科大学, 医学部, 講師 (10165128) 菅沼雅美埼玉県立がんセンター, 研究所, 研究員 (20196695) 島礼国立がんセンター, 研究所, 室長 (10196462) 田村眞理東北大学, 加齢医学研究所, 教授 (20124604) 武田誠郎広島大学, 医学部, 教授 (40030853)
キーワード	プロテインホスファターゼ / セリン / スレオニンホスファターゼ / チロシンホスファターゼ / 発癌 / 癌形質 / 細胞増殖 / 蛋白脱リン酸 / 遺伝子発現
研究概要	菊地は,肝/肝癌系でPP1,PP2A,PP2Cの癌性異変を系統的に解析し,また正常肝細胞での動態を検討した。腹水肝癌細胞では,検索した十数種の細胞株全てにおいて,例外なくPP1特にその1イソホームPP1αの特異的なmRNAおよび酵素蛋白の増量を認めた。PP2Aは大方不変,PP2Cは逆に減少していた。これに対し,肝細胞では,EGF刺激により,G1/S期に核内PP1活性が約2.5倍に特異的に上昇し,この上昇は,増殖を抑制するTGFβの存在下で完全に抑えられた。このPP1活性の上昇は,酵素蛋白の上昇を伴わず,翻訳後の修飾あるいは調節サブユニットの影響が考えられる。武田は,PP2Aの72-74kDa調節サブユニットの組織分布を調べた(未発表)。田村は,マウスのPP2Cα cDNA,およびマウスのPP2Cβの5種類のイソホーム(PP2Cβ-1,-2,-3,-4,-5)をコードするcDNAを単離し,それらの解析を行った。伊藤は,新しいホロエンザイムPP1-Mを精製し,cDNAクローニングによるアミノ酸一次構造を決定した。菅沼は,海綿(Agelas axifera)の抽出物がPP2Aのアッセイ系で約3倍に脱リン酸化を亢進することを認め,これをagelasine-Bと同定した。島は,ラット脳から新しいプロテインホスファターゼPPHのcDNAと考えられるクローン(2.1kb)を単離した。久野は,選択的スプライシングにより生じるカルシニューリン(PP2B)制御サブユニットのcDNAクローニングを行った。日野田は,新しいPTP,LC-PTPをクローニングした。矢倉は,Bリンパ球のシグナル伝達におけるチロシンホスファターゼの役割を解析した。野口は,新種のPTPase,RKPTPの全翻訳領域を含むcDNAを解析した。武内は,新規のBand4.1型チロシンホスファターゼを3分子同定することに成功した。揚河は,肺癌患者におけるサイトカインネットワークの解析を行った。

研究成果
(27件)

すべてその他

すべて文献書誌 (27件)

[文献書誌] Kakinoki,Y.: "TGFβ1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase activity at the G1/S transition of hepatocyte proliferation." FEBS Lett.352. 356-360 (1994)
[文献書誌] Takizawa,N.: "Selective increases in isoform PP1α of type-1 protein phosphatase in ascites hepatoma cells." Jpn.J.Cancer Res.85. 274-278 (1994)
[文献書誌] Saadat,M.: "Gene expressin of protein phosphatases in rat ascites hepatoma cell lines." Cancer Detect.Prev.18. 115-122 (1994)
[文献書誌] Takizawa,N.: "Tissue distribution of isoform of type-1 Protein phosphatase PP1 in mouse tissues and its diabetic alterations." J.Biochem.116. 411-415 (1994)
[文献書誌] Igarashi,H.: "B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell mature B cell." J.Immunol.153. 2381-2393 (1994)
[文献書誌] Matsuzawa,S.: "TGFβ1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase Thyrsiferyl 23-acetate is a novel specific inhibitor of protein phosphatase PP2A." FEBS Lett.356. 272-274 (1994)
[文献書誌] Murakami,T.: "Characterization of multiple molecular forms of Mg^<2+>-dependent protein phosphatase from Saccharomyces cerevisiae." J.Biochem.115. 762-766 (1994)
[文献書誌] Kato,S.: "The cDNA sequence encoding mouse Mg^<2+>-dependent protein phosphatase α." Gene. 145. 311-312 (1994)
[文献書誌] Yokoyama,N.: "Involvement of type 2C phosphatase in the dephosphorylation of 26kDa phosphoprotein in rat parotid acinar cells." Biochem.Biophys.Res.Commun.200. 467-503 (1994)
[文献書誌] Simizu,H.: "Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase." J.Biol.Chem.269. 30407-30411 (1994)
[文献書誌] Inagaki,N.: "Spatiotemporal distribution of protein kinase and phosphatase activites." Trends.Biochem.Sci.277. 448-452 (1994)
[文献書誌] Fujiki,H.: "Tumor necrosis factor-α、a new tumor promoter,engendered by biochemical studies of okadaic acid." J.Biochem.115. 1-5 (1994)
[文献書誌] Nishiwaki,R.: "Two significant aspects of microcystin-LR:specific binding and liver specificity." Cancer Lett.83. 283-289 (1994)
[文献書誌] Ohta,T.: "Nodularin,a potent inhibitor of protein phosphatases 1 and 2A,is a new environmental carcinogen in male F344 rat liver." Cancer Res.54. 4448-4453 (1994)
[文献書誌] Chun,Y.S.: "PP1y2,a testis specific serine/threonine protein phosphatase type 1 catalytic subunits,is associated with GRP 78,a member of hsp 70 family." Proc.Natl.Acad.USA. 91. 3319-3323 (1994)
[文献書誌] Zhang,Z.: "A mutant of protein phosphatase-1 that exhibits altered toxin sensitivity." J.Biol.Chem.269. 16997-17000 (1994)
[文献書誌] Shima,H.: "Detection of PP2A α gene mutation in okadaic acid resistant cell line." Proc.Natl.Acad.Sci.USA. 91. 9267-9271 (1994)
[文献書誌] Chang,C,-D.: "cDNA cloning of an altematively spliced isoform of the regulatory subunit of Ca^<2+>/calmodulin-dependent protein phosphatase(calcineurin B α 2)." Biochim.Biophys.Acta. 1217. 174-180 (1994)
[文献書誌] Tamura,K.: "Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin." Biochem.Biophys.Res.Commun.202. 437-443 (1994)
[文献書誌] Takekawa,M.: "Chromosomal localization of the protein tyrosine phosphatase G1 gene and characterzation of the aberrant transcripts in human colon cancer cells." FEBS Lett.339. 222-228 (1994)
[文献書誌] Adachi,M.: "Induction of protein tyrosine phosphatase LC-PTP by IL-2 in human T cells." FEBS Lett.338. 47-52 (1994)
[文献書誌] Ikuta,S.: "Expression of cytoskeletal-assosiated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma." J.Gastroenterol. 29. 727-732 (1994)
[文献書誌] Yakura,H.: "The role of protein tyrosine phosphatases in lymphocyte activation and differentiation." Crit.Rev.Immunol.印刷中.
[文献書誌] Mizuno,K.: "Developmental regulation of gene expression for the MPTP δ isoforms in the central nervous system and the immune system." FEBS Lett.355. 223-228 (1994)
[文献書誌] Moriyama,T.: "cDNA cloning of a cytosolic protein tyrosine phosphatase(RKPTP)from rat kidney." FEBS Lett.353. 305-308 (1994)
[文献書誌] Takeuchi,K.: "Pertubation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members." J.Cell.Biol.125. 1371-1384 (1994)
[文献書誌] Yanagawa,H.: "Serum levels of interleukin-6 in patients with lung cancer." Brit.J.Cancer. (印刷中).

1994 年度 実績報告書

発癌過程ならびに癌細胞形質の発現におけるプロテインホスファターゼの意義

研究代表者

菊地 九二三 北海道大学, 免疫科学研究所, 教授 (20006117)

研究成果

[文献書誌] Kakinoki,Y.: "TGFβ1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase activity at the G1/S transition of hepatocyte proliferation." FEBS Lett.352. 356-360 (1994)

[文献書誌] Takizawa,N.: "Selective increases in isoform PP1α of type-1 protein phosphatase in ascites hepatoma cells." Jpn.J.Cancer Res.85. 274-278 (1994)

[文献書誌] Saadat,M.: "Gene expressin of protein phosphatases in rat ascites hepatoma cell lines." Cancer Detect.Prev.18. 115-122 (1994)

[文献書誌] Takizawa,N.: "Tissue distribution of isoform of type-1 Protein phosphatase PP1 in mouse tissues and its diabetic alterations." J.Biochem.116. 411-415 (1994)

[文献書誌] Igarashi,H.: "B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell mature B cell." J.Immunol.153. 2381-2393 (1994)

[文献書誌] Matsuzawa,S.: "TGFβ1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase Thyrsiferyl 23-acetate is a novel specific inhibitor of protein phosphatase PP2A." FEBS Lett.356. 272-274 (1994)

[文献書誌] Murakami,T.: "Characterization of multiple molecular forms of Mg^<2+>-dependent protein phosphatase from Saccharomyces cerevisiae." J.Biochem.115. 762-766 (1994)

[文献書誌] Kato,S.: "The cDNA sequence encoding mouse Mg^<2+>-dependent protein phosphatase α." Gene. 145. 311-312 (1994)

[文献書誌] Yokoyama,N.: "Involvement of type 2C phosphatase in the dephosphorylation of 26kDa phosphoprotein in rat parotid acinar cells." Biochem.Biophys.Res.Commun.200. 467-503 (1994)

[文献書誌] Simizu,H.: "Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase." J.Biol.Chem.269. 30407-30411 (1994)

[文献書誌] Inagaki,N.: "Spatiotemporal distribution of protein kinase and phosphatase activites." Trends.Biochem.Sci.277. 448-452 (1994)

[文献書誌] Fujiki,H.: "Tumor necrosis factor-α、a new tumor promoter,engendered by biochemical studies of okadaic acid." J.Biochem.115. 1-5 (1994)

[文献書誌] Nishiwaki,R.: "Two significant aspects of microcystin-LR:specific binding and liver specificity." Cancer Lett.83. 283-289 (1994)

[文献書誌] Ohta,T.: "Nodularin,a potent inhibitor of protein phosphatases 1 and 2A,is a new environmental carcinogen in male F344 rat liver." Cancer Res.54. 4448-4453 (1994)

[文献書誌] Chun,Y.S.: "PP1y2,a testis specific serine/threonine protein phosphatase type 1 catalytic subunits,is associated with GRP 78,a member of hsp 70 family." Proc.Natl.Acad.USA. 91. 3319-3323 (1994)

[文献書誌] Zhang,Z.: "A mutant of protein phosphatase-1 that exhibits altered toxin sensitivity." J.Biol.Chem.269. 16997-17000 (1994)

[文献書誌] Shima,H.: "Detection of PP2A α gene mutation in okadaic acid resistant cell line." Proc.Natl.Acad.Sci.USA. 91. 9267-9271 (1994)

[文献書誌] Chang,C,-D.: "cDNA cloning of an altematively spliced isoform of the regulatory subunit of Ca^<2+>/calmodulin-dependent protein phosphatase(calcineurin B α 2)." Biochim.Biophys.Acta. 1217. 174-180 (1994)

[文献書誌] Tamura,K.: "Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin." Biochem.Biophys.Res.Commun.202. 437-443 (1994)

[文献書誌] Takekawa,M.: "Chromosomal localization of the protein tyrosine phosphatase G1 gene and characterzation of the aberrant transcripts in human colon cancer cells." FEBS Lett.339. 222-228 (1994)

[文献書誌] Adachi,M.: "Induction of protein tyrosine phosphatase LC-PTP by IL-2 in human T cells." FEBS Lett.338. 47-52 (1994)

[文献書誌] Ikuta,S.: "Expression of cytoskeletal-assosiated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma." J.Gastroenterol. 29. 727-732 (1994)

[文献書誌] Yakura,H.: "The role of protein tyrosine phosphatases in lymphocyte activation and differentiation." Crit.Rev.Immunol.印刷中.

[文献書誌] Mizuno,K.: "Developmental regulation of gene expression for the MPTP δ isoforms in the central nervous system and the immune system." FEBS Lett.355. 223-228 (1994)

[文献書誌] Moriyama,T.: "cDNA cloning of a cytosolic protein tyrosine phosphatase(RKPTP)from rat kidney." FEBS Lett.353. 305-308 (1994)

[文献書誌] Takeuchi,K.: "Pertubation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members." J.Cell.Biol.125. 1371-1384 (1994)

[文献書誌] Yanagawa,H.: "Serum levels of interleukin-6 in patients with lung cancer." Brit.J.Cancer. (印刷中).

1994 年度実績報告書

菊地九二三北海道大学, 免疫科学研究所, 教授 (20006117)